Genomic Alterations and Targeted Therapy in Gastric and Esophageal Adenocarcinoma

Purpose: Gastric and esophageal adenocarcinomas are common and aggressive malignancies. Systemic therapy for these tumors is based primarily on cytotoxic chemotherapy, but outcomes remain poor. Precision medicine, where treatments are tailored to specific molecular abnormalities of tumors, holds great promise for improving outcomes in this disease. Methods: A search was performed in PubMed to identify studies that have characterized the molecular basis of gastric and esophageal adenocarcinoma, as well as clinical trials exploring targeted therapies in this disease. Findings: Recent genomic studies have identified potentially targetable genomic alterations in gastroesophageal adenocarcinoma. Specifically, The Cancer Genome Atlas study defined 4 subgroups of gastric cancer, each harboring distinct genomic features. However, development of targeted therapies for gastroesophageal cancer has been challenging. The only biomarker-driven therapy in clinical practice, trastuzumab for the similar to 15% of patients with human epidermal growth factor receptor 2-positive disease, is modestly effective, extending median overall survival by 2.7 months. Clinical trials of other targeted therapies, including epidermal growth factor receptor, fibroblast growth factor receptor 2, and MET inhibitors, have had disappointing results so far. (C) 2016 Elsevier HS Journals, Inc. All rights reserved.